{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T14:38:36Z","timestamp":1794321516365,"version":"4.9.0"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000072","name":"U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R00-DE024178"],"award-info":[{"award-number":["R00-DE024178"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01-DK116317"],"award-info":[{"award-number":["U01-DK116317"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30-DK020579"],"award-info":[{"award-number":["P30-DK020579"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30-DK020593"],"award-info":[{"award-number":["P30-DK020593"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01-DK132073"],"award-info":[{"award-number":["R01-DK132073"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK137798"],"award-info":[{"award-number":["DK137798"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R56-AR081251"],"award-info":[{"award-number":["R56-AR081251"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30-AR074992"],"award-info":[{"award-number":["P30-AR074992"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR075773"],"award-info":[{"award-number":["AR075773"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["RF1-AG066905"],"award-info":[{"award-number":["RF1-AG066905"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"U.S. Department of Health & Human Services | NIH | National Institute on Aging","doi-asserted-by":"publisher","award":["AG069795"],"award-info":[{"award-number":["AG069795"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Metab"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Several adipose depots, including constitutive bone marrow adipose tissue, resist conventional lipolytic cues. However, under starvation, wasting or cachexia, the body eventually catabolizes stable adipocytes through unknown mechanisms. Here we developed a mouse model of brain-evoked depletion of all fat, including stable constitutive bone marrow adipose tissue, independent of food intake, to study this phenomenon. Genetic, surgical and chemical approaches demonstrated that catabolism of stable adipocytes required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system and catecholamines. Instead, concurrent hypoglycaemia and hypoinsulinaemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent lipolysis via downregulation of cell-autonomous lipolytic inhibitors including G0s2. This was also sufficient to delipidate classical adipose depots and was recapitulated in tumour-associated cachexic mice. Overall, this defines unique adaptations of stable adipocytes to resist lipolysis in healthy states while isolating a potent catecholamine-independent neurosystemic pathway by which the body can rapidly catabolize all adipose tissues.<\/jats:p>","DOI":"10.1038\/s42255-025-01424-5","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:02:32Z","timestamp":1767866552000},"page":"96-115","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A catecholamine-independent pathway controlling adaptive adipocyte lipolysis"],"prefix":"10.1038","volume":"8","author":[{"given":"Xiao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreejith S.","family":"Panicker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Bollinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anurag","family":"Majumdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami","family":"Kheireddine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lila F.","family":"Dabill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-1803","authenticated-orcid":false,"given":"Brian","family":"Kleiboeker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2188-7558","authenticated-orcid":false,"given":"Fengrui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9359-6525","authenticated-orcid":false,"given":"Yongbin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristann L.","family":"Magee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3680-0061","authenticated-orcid":false,"given":"Brian S.","family":"Learman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kepecs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9268-3993","authenticated-orcid":false,"given":"Gretchen A.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3646-0004","authenticated-orcid":false,"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6246-9862","authenticated-orcid":false,"given":"Irfan J.","family":"Lodhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6907-7960","authenticated-orcid":false,"given":"Ormond A.","family":"MacDougald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1551-3816","authenticated-orcid":false,"given":"Erica L.","family":"Scheller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"1424_CR1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.plefa.2005.04.010","volume":"73","author":"S Cinti","year":"2005","unstructured":"Cinti, S. The adipose organ. Prostaglandins Leukot. Essent. Fat. Acids 73, 9\u201315 (2005).","journal-title":"Essent. Fat. Acids"},{"key":"1424_CR2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8808","volume":"6","author":"EL Scheller","year":"2015","unstructured":"Scheller, E. L. et al. Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues. Nat. Commun. 6, 7808 (2015).","journal-title":"Nat. Commun."},{"key":"1424_CR3","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.bone.2018.01.016","volume":"118","author":"EL Scheller","year":"2019","unstructured":"Scheller, E. L. et al. Bone marrow adipocytes resist lipolysis and remodeling in response to \u03b2-adrenergic stimulation. Bone 118, 32\u201341 (2019).","journal-title":"Bone"},{"key":"1424_CR4","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.cmet.2017.12.002","volume":"27","author":"RK Zwick","year":"2018","unstructured":"Zwick, R. K., Guerrero-Juarez, C. F., Horsley, V. & Plikus, M. V. Anatomical, physiological, and functional diversity of adipose tissue. Cell Metab. 27, 68\u201383 (2018).","journal-title":"Cell Metab."},{"key":"1424_CR5","doi-asserted-by":"publisher","first-page":"1422869","DOI":"10.3389\/fendo.2024.1422869","volume":"15","author":"R Ojala","year":"2024","unstructured":"Ojala, R. et al. Evaluation of bone marrow glucose uptake and adiposity in male rats after diet and exercise interventions. Front. Endocrinol. 15, 1422869 (2024).","journal-title":"Front. Endocrinol."},{"key":"1424_CR6","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.cmet.2014.06.003","volume":"20","author":"WP Cawthorn","year":"2014","unstructured":"Cawthorn, W. P. et al. Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction. Cell Metab. 20, 368\u2013375 (2014).","journal-title":"Cell Metab."},{"key":"1424_CR7","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1007\/BF01921701","volume":"30","author":"M Tavassoli","year":"1974","unstructured":"Tavassoli, M. Differential response of bone marrow and extramedullary adipose cells to starvation. Experientia 30, 424\u2013425 (1974).","journal-title":"Experientia"},{"key":"1424_CR8","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/nyas.12327","volume":"1311","author":"EL Scheller","year":"2014","unstructured":"Scheller, E. L. & Rosen, C. J. What\u2019s the matter with MAT? Marrow adipose tissue, metabolism, and skeletal health. Ann. N. Y. Acad. Sci. 1311, 14\u201330 (2014).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"1424_CR9","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1053\/j.semnuclmed.2007.01.002","volume":"37","author":"JS Blebea","year":"2007","unstructured":"Blebea, J. S. et al. Structural and functional imaging of normal bone marrow and evaluation of its age-related changes. Semin. Nucl. Med. 37, 185\u2013194 (2007).","journal-title":"Semin. Nucl. Med."},{"key":"1424_CR10","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/ajhb.21202","volume":"23","author":"MJ Devlin","year":"2011","unstructured":"Devlin, M. J. Why does starvation make bones fat?. Am. J. Hum. Biol. 23, 577\u2013585 (2011).","journal-title":"Am. J. Hum. Biol."},{"key":"1424_CR11","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/S0022-2275(20)37320-X","volume":"22","author":"MA Tran","year":"1981","unstructured":"Tran, M. A., Dang, T. L. & Berlan, M. Effects of catecholamines on free fatty acid release from bone marrow adipose tissue. J. Lipid Res. 22, 1271\u20131276 (1981).","journal-title":"J. Lipid Res."},{"key":"1424_CR12","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1016\/j.celrep.2019.12.089","volume":"30","author":"C Attan\u00e9","year":"2020","unstructured":"Attan\u00e9, C. et al. Human bone marrow is comprised of adipocytes with specific lipid metabolism. Cell Rep. 30, 949\u2013958 (2020).","journal-title":"Cell Rep."},{"key":"1424_CR13","first-page":"16","volume":"100","author":"M Tavassoli","year":"1976","unstructured":"Tavassoli, M. Marrow adipose cells. Histochemical identification of labile and stable components. Arch. Pathol. Lab. Med. 100, 16\u201318 (1976).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"1424_CR14","doi-asserted-by":"publisher","first-page":"E977","DOI":"10.1152\/ajpendo.00183.2009","volume":"297","author":"S Cinti","year":"2009","unstructured":"Cinti, S. Transdifferentiation properties of adipocytes in the adipose organ. Am. J. Physiol. Endocrinol. Metab. 297, E977\u2013E986 (2009).","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"1424_CR15","doi-asserted-by":"crossref","unstructured":"Zhang, X., Tian, L., Majumdar, A. & Scheller, E. L. in Comprehensive Physiology (ed. Prakash, Y. S.) Vol. 14, 5521\u20135579 (Wiley, 2024).","DOI":"10.1002\/j.2040-4603.2024.tb00300.x"},{"key":"1424_CR16","doi-asserted-by":"publisher","first-page":"e66275","DOI":"10.7554\/eLife.66275","volume":"10","author":"X Zhang","year":"2021","unstructured":"Zhang, X. et al. A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease. eLife 10, e66275 (2021).","journal-title":"eLife"},{"key":"1424_CR17","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1309\/2Y7X-YDXK-006B-XLT2","volume":"118","author":"E Abella","year":"2002","unstructured":"Abella, E. et al. Bone marrow changes in anorexia nervosa are correlated with the amount of weight loss and not with other clinical findings. Am. J. Clin. Pathol. 118, 582\u2013588 (2002).","journal-title":"Am. J. Clin. Pathol."},{"key":"1424_CR18","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/0003-9861(54)90242-8","volume":"53","author":"JD Evans","year":"1954","unstructured":"Evans, J. D., Riemenschneider, R. W. & Herb, S. F. Fat composition and in vitro oxygen consumption of marrow from fed and fasted rabbits. Arch. Biochem. Biophys. 53, 157\u2013166 (1954).","journal-title":"Arch. Biochem. Biophys."},{"key":"1424_CR19","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1097\/00000478-200001000-00007","volume":"24","author":"J B\u00f6hm","year":"2000","unstructured":"B\u00f6hm, J. Gelatinous transformation of the bone marrow: the spectrum of underlying diseases. Am. J. Surg. Pathol. 24, 56\u201365 (2000).","journal-title":"Am. J. Surg. Pathol."},{"key":"1424_CR20","doi-asserted-by":"publisher","first-page":"2771","DOI":"10.1007\/s00330-015-3692-5","volume":"25","author":"RD Boutin","year":"2015","unstructured":"Boutin, R. D. et al. MRI findings of serous atrophy of bone marrow and associated complications. Eur. Radiol. 25, 2771\u20132778 (2015).","journal-title":"Eur. Radiol."},{"key":"1424_CR21","doi-asserted-by":"publisher","first-page":"e78496","DOI":"10.7554\/eLife.78496","volume":"11","author":"Z Li","year":"2022","unstructured":"Li, Z. et al. Lipolysis of bone marrow adipocytes is required to fuel bone and the marrow niche during energy deficits. eLife 11, e78496 (2022).","journal-title":"eLife"},{"key":"1424_CR22","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s00441-006-0312-3","volume":"327","author":"MW Hamrick","year":"2007","unstructured":"Hamrick, M. W. et al. Injections of leptin into rat ventromedial hypothalamus increase adipocyte apoptosis in peripheral fat and in bone marrow. Cell Tissue Res. 327, 133\u2013141 (2007).","journal-title":"Cell Tissue Res."},{"key":"1424_CR23","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/S0092-8674(02)01049-8","volume":"111","author":"S Takeda","year":"2002","unstructured":"Takeda, S. et al. Leptin regulates bone formation via the sympathetic nervous system. Cell 111, 305\u2013317 (2002).","journal-title":"Cell"},{"key":"1424_CR24","doi-asserted-by":"publisher","first-page":"R1499","DOI":"10.1152\/ajpregu.00335.2015","volume":"309","author":"RBS Harris","year":"2015","unstructured":"Harris, R. B. S. In vivo evidence for unidentified leptin-induced circulating factors that control white fat mass. Am. J. Physiol. Regul. Integr. Comp. Physiol. 309, R1499\u2013R1511 (2015).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"1424_CR25","doi-asserted-by":"publisher","first-page":"R92","DOI":"10.1152\/ajpregu.00858.2004","volume":"289","author":"CR Rooks","year":"2005","unstructured":"Rooks, C. R. et al. Sympathetic denervation does not prevent a reduction in fat pad size of rats or mice treated with peripherally administered leptin. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R92\u2013R102 (2005).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"1424_CR26","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.cell.2015.08.055","volume":"163","author":"W Zeng","year":"2015","unstructured":"Zeng, W. et al. Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell 163, 84\u201394 (2015).","journal-title":"Cell"},{"key":"1424_CR27","doi-asserted-by":"publisher","first-page":"R790","DOI":"10.1152\/ajpregu.2000.278.3.R790","volume":"278","author":"J Rafael","year":"2000","unstructured":"Rafael, J. & Herling, A. W. Leptin effect in ob\/ob mice under thermoneutral conditions depends not necessarily on central satiation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 278, R790\u2013R795 (2000).","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"1424_CR28","first-page":"243","volume":"16","author":"Y Wang","year":"2013","unstructured":"Wang, Y. & Pessin, J. E. Mechanisms for fiber-type specificity of skeletal muscle atrophy. Curr. Opin. Clin. Nutr. Metab. Care 16, 243\u2013250 (2013).","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"1424_CR29","doi-asserted-by":"publisher","first-page":"3484","DOI":"10.1172\/JCI24059","volume":"115","author":"C de Luca","year":"2005","unstructured":"de Luca, C. et al. Complete rescue of obesity, diabetes, and infertility in db\/db mice by neuron-specific LEPR-B transgenes. J. Clin. Invest. 115, 3484\u20133493 (2005).","journal-title":"J. Clin. Invest."},{"key":"1424_CR30","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1172\/JCI200113914","volume":"108","author":"P Cohen","year":"2001","unstructured":"Cohen, P. et al. Selective deletion of leptin receptor in neurons leads to obesity. J. Clin. Invest. 108, 1113\u20131121 (2001).","journal-title":"J. Clin. Invest."},{"key":"1424_CR31","doi-asserted-by":"publisher","first-page":"3987","DOI":"10.1210\/en.2007-0261","volume":"148","author":"K Guo","year":"2007","unstructured":"Guo, K. et al. Disruption of peripheral leptin signaling in mice results in hyperleptinemia without associated metabolic abnormalities. Endocrinology 148, 3987\u20133997 (2007).","journal-title":"Endocrinology"},{"key":"1424_CR32","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1002\/jbmr.4273","volume":"36","author":"MR Lorenz","year":"2021","unstructured":"Lorenz, M. R., Brazill, J. M., Beeve, A. T., Shen, I. & Scheller, E. L. A neuroskeletal atlas: spatial mapping and contextualization of axon subtypes innervating the long bones of C3H and B6 mice. J. Bone Miner. Res. 36, 1012\u20131025 (2021).","journal-title":"J. Bone Miner. Res."},{"key":"1424_CR33","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1161\/01.HYP.5.4.552","volume":"5","author":"DS Goldstein","year":"1983","unstructured":"Goldstein, D. S., McCarty, R., Polinsky, R. J. & Kopin, I. J. Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension 5, 552\u2013559 (1983).","journal-title":"Hypertension"},{"key":"1424_CR34","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1016\/0024-3205(93)90565-K","volume":"53","author":"A Takahashi","year":"1993","unstructured":"Takahashi, A., Ikarashi, Y., Ishimaru, H. & Maruyama, Y. Compensation between sympathetic nerves and adrenal medullary activity: effects of adrenodemedullation and chemical sympathectomy on catecholamine turnover. Life Sci. 53, 1567\u20131572 (1993).","journal-title":"Life Sci."},{"key":"1424_CR35","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.yfrne.2014.04.001","volume":"35","author":"TJ Bartness","year":"2014","unstructured":"Bartness, T. J., Liu, Y., Shrestha, Y. B. & Ryu, V. Neural innervation of white adipose tissue and the control of lipolysis. Front. Neuroendocrinol. 35, 473\u2013493 (2014).","journal-title":"Front. Neuroendocrinol."},{"key":"1424_CR36","doi-asserted-by":"publisher","first-page":"12912","DOI":"10.1073\/pnas.91.26.12912","volume":"91","author":"J Bergquist","year":"1994","unstructured":"Bergquist, J., Tarkowski, A., Ekman, R. & Ewing, A. Discovery of endogenous catecholamines in lymphocytes and evidence for catecholamine regulation of lymphocyte function via an autocrine loop. Proc. Natl Acad. Sci. USA 91, 12912\u201312916 (1994).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1424_CR37","unstructured":"Khalil, B., Rosani, A. & Warrington, S. J. Physiology, catecholamines. in StatPearls Bookshelf ID: NBK507716 (StatPearls, 2025)."},{"key":"1424_CR38","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1038\/374643a0","volume":"374","author":"SA Thomas","year":"1995","unstructured":"Thomas, S. A., Matsumoto, A. M. & Palmiter, R. D. Noradrenaline is essential for mouse fetal development. Nature 374, 643\u2013646 (1995).","journal-title":"Nature"},{"key":"1424_CR39","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/978-1-59745-104-8_7","volume":"455","author":"GJ Pettway","year":"2008","unstructured":"Pettway, G. J. & McCauley, L. K. Ossicle and vossicle implant model systems. Methods Mol. Biol. 455, 101\u2013110 (2008).","journal-title":"Methods Mol. Biol."},{"key":"1424_CR40","unstructured":"Peterson, C. Study: deer\u2019s lifelong fate is affected by mother\u2019s health at birth. WyoFile https:\/\/wyofile.com\/study-deers-lifelong-fate-is-affected-by-mothers-health-at-birth\/ (2023)."},{"key":"1424_CR41","unstructured":"Ahmed, F. W., Majeed, M. S. & Kirresh, O. Non-diabetic hypoglycemia. in StatPearls Bookshelf ID: NBK573079 (StatPearls, 2023)."},{"key":"1424_CR42","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1210\/endo.139.2.5908","volume":"139","author":"H Qian","year":"1998","unstructured":"Qian, H. et al. Brain administration of leptin causes deletion of adipocytes by apoptosis. Endocrinology 139, 791\u2013794 (1998).","journal-title":"Endocrinology"},{"key":"1424_CR43","doi-asserted-by":"publisher","first-page":"R199","DOI":"10.1530\/JME-13-0277","volume":"52","author":"TS Nielsen","year":"2014","unstructured":"Nielsen, T. S., Jessen, N., J\u00f8rgensen, J. O. L., M\u00f8ller, N. & Lund, S. Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease. J. Mol. Endocrinol. 52, R199\u2013R222 (2014).","journal-title":"J. Mol. Endocrinol."},{"key":"1424_CR44","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/nm1775","volume":"14","author":"C Buettner","year":"2008","unstructured":"Buettner, C. et al. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat. Med. 14, 667\u2013675 (2008).","journal-title":"Nat. Med."},{"key":"1424_CR45","doi-asserted-by":"publisher","first-page":"20952","DOI":"10.1016\/S0021-9258(17)45309-9","volume":"265","author":"DR Nussenzveig","year":"1990","unstructured":"Nussenzveig, D. R., Lewicki, J. A. & Maack, T. Cellular mechanisms of the clearance function of type C receptors of atrial natriuretic factor. J. Biol. Chem. 265, 20952\u201320958 (1990).","journal-title":"J. Biol. Chem."},{"key":"1424_CR46","doi-asserted-by":"publisher","first-page":"48617","DOI":"10.1074\/jbc.M303713200","volume":"278","author":"C Sengenes","year":"2003","unstructured":"Sengenes, C. et al. Involvement of a cGMP-dependent pathway in the natriuretic peptide-mediated hormone-sensitive lipase phosphorylation in human adipocytes. J. Biol. Chem. 278, 48617\u201348626 (2003).","journal-title":"J. Biol. Chem."},{"key":"1424_CR47","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1096\/fasebj.14.10.1345","volume":"14","author":"C Sengen\u00e8s","year":"2000","unstructured":"Sengen\u00e8s, C., Berlan, M., De Glisezinski, I., Lafontan, M. & Galitzky, J. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J. 14, 1345\u20131351 (2000).","journal-title":"FASEB J."},{"key":"1424_CR48","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1097\/00004872-199511000-00004","volume":"13","author":"R Sarzani","year":"1995","unstructured":"Sarzani, R. et al. Fasting inhibits natriuretic peptides clearance receptor expression in rat adipose tissue. J. Hypertens. 13, 1241\u20131246 (1995).","journal-title":"J. Hypertens."},{"key":"1424_CR49","doi-asserted-by":"publisher","first-page":"e2309967120","DOI":"10.1073\/pnas.2309967120","volume":"120","author":"RC Adam","year":"2023","unstructured":"Adam, R. C. et al. Activin E-ACVR1C cross talk controls energy storage via suppression of adipose lipolysis in mice. Proc. Natl Acad. Sci. USA 120, e2309967120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1424_CR50","doi-asserted-by":"publisher","first-page":"115","DOI":"10.2337\/db12-0295","volume":"62","author":"S Yogosawa","year":"2013","unstructured":"Yogosawa, S., Mizutani, S., Ogawa, Y. & Izumi, T. Activin receptor-like kinase 7 suppresses lipolysis to accumulate fat in obesity through downregulation of peroxisome proliferator-activated receptor \u03b3 and C\/EBP\u03b1. Diabetes 62, 115\u2013123 (2013).","journal-title":"Diabetes"},{"key":"1424_CR51","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.cmet.2010.02.003","volume":"11","author":"X Yang","year":"2010","unstructured":"Yang, X. et al. The G(0)\/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab. 11, 194\u2013205 (2010).","journal-title":"Cell Metab."},{"key":"1424_CR52","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/j.bbalip.2017.06.007","volume":"1862","author":"X Zhang","year":"2017","unstructured":"Zhang, X., Heckmann, B. L., Campbell, L. E. & Liu, J. G0S2: a small giant controller of lipolysis and adipose-liver fatty acid flux. Biochim. Biophys. Acta Mol. Cell. Biol. Lipids 1862, 1146\u20131154 (2017).","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"1424_CR53","doi-asserted-by":"publisher","DOI":"10.1172\/JCI181754","author":"Y Chen","year":"2025","unstructured":"Chen, Y. et al. Absence of intracellular lipolytic inhibitor G0S2 enhances intravascular triglyceride clearance and abolishes diet-induced hypertriglyceridemia. J. Clin. Invest. https:\/\/doi.org\/10.1172\/JCI181754 (2025).","journal-title":"J. Clin. Invest."},{"key":"1424_CR54","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/0304-4165(85)90248-X","volume":"838","author":"Y Hakeda","year":"1985","unstructured":"Hakeda, Y. et al. Induction of osteoblastic cell differentiation by forskolin. Stimulation of cyclic AMP production and alkaline phosphatase activity. Biochim. Biophys. Acta Gen. Subj. 838, 49\u201353 (1985).","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"1424_CR55","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1093\/oxfordjournals.jbchem.a122016","volume":"101","author":"Y Hakeda","year":"1987","unstructured":"Hakeda, Y. et al. Effect of forskolin on collagen production in clonal osteoblastic MC3T3-E1 cells. J. Biochem. 101, 1463\u20131469 (1987).","journal-title":"J. Biochem."},{"key":"1424_CR56","first-page":"2290","volume":"50","author":"Y Tanaka","year":"1990","unstructured":"Tanaka, Y. et al. Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice. Cancer Res. 50, 2290\u20132295 (1990).","journal-title":"Cancer Res."},{"key":"1424_CR57","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1210\/jc.2012-3634","volume":"98","author":"PK Fazeli","year":"2013","unstructured":"Fazeli, P. K. et al. Marrow fat and bone\u2014new perspectives. J. Clin. Endocrinol. Metab. 98, 935\u2013945 (2013).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1424_CR58","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1182\/blood.V43.1.33.33","volume":"43","author":"M Tavassoli","year":"1974","unstructured":"Tavassoli, M., Maniatis, A. & Crosby, W. H. Induction of sustained hemopoiesis in fatty marrow. Blood 43, 33\u201338 (1974).","journal-title":"Blood"},{"key":"1424_CR59","doi-asserted-by":"publisher","first-page":"163","DOI":"10.21037\/apm-22-1422","volume":"12","author":"X Yang","year":"2023","unstructured":"Yang, X., Liu, X., Wang, L., Xu, J. & Wen, J. Hypoglycemia on admission in patients with acute on chronic liver failure: a retrospective cohort analyzing the current situation, risk factors, and associations with prognosis. Ann. Palliat. Med. 12, 163\u2013170 (2023).","journal-title":"Ann. Palliat. Med."},{"key":"1424_CR60","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1536\/ihj.20-134","volume":"61","author":"Y Teshima","year":"2020","unstructured":"Teshima, Y. et al. Potential risk of hypoglycemia in patients with heart failure. Int. Heart J. 61, 776\u2013780 (2020).","journal-title":"Int. Heart J."},{"key":"1424_CR61","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1185\/03007997709109340","volume":"4","author":"HA Hedayati","year":"1977","unstructured":"Hedayati, H. A. & Beheshti, M. Profound spontaneous hypoglycaemia in congestive heart failure. Curr. Med. Res. Opin. 4, 501\u2013504 (1977).","journal-title":"Curr. Med. Res. Opin."},{"key":"1424_CR62","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1001\/archinte.1990.00390160134027","volume":"150","author":"LM Rich","year":"1990","unstructured":"Rich, L. M. Hypoglycemic coma in anorexia nervosa. Arch. Intern. Med. 150, 894\u2013895 (1990).","journal-title":"Arch. Intern. Med."},{"key":"1424_CR63","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1093\/jnci\/89.23.1763","volume":"89","author":"MJ Tisdale","year":"1997","unstructured":"Tisdale, M. J. Biology of cachexia. J. Natl Cancer Inst. 89, 1763\u20131773 (1997).","journal-title":"J. Natl Cancer Inst."},{"key":"1424_CR64","first-page":"1226","volume":"17","author":"J Varga","year":"1990","unstructured":"Varga, J., Lopatin, M. & Boden, G. Hypoglycemia due to antiinsulin receptor antibodies in systemic lupus erythematosus. J. Rheumatol. 17, 1226\u20131229 (1990).","journal-title":"J. Rheumatol."},{"key":"1424_CR65","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1016\/j.molmet.2017.04.010","volume":"6","author":"BB Boland","year":"2017","unstructured":"Boland, B. B., Rhodes, C. J. & Grimsby, J. S. The dynamic plasticity of insulin production in \u03b2-cells. Mol. Metab. 6, 958\u2013973 (2017).","journal-title":"Mol. Metab."},{"key":"1424_CR66","unstructured":"Mathew, P. & Thoppil, D. Hypoglycemia. in StatPearls Bookshelf ID: NBK534841 (StatPearls, 2018)."},{"key":"1424_CR67","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1210\/edrv-12-4-356","volume":"12","author":"JE Gerich","year":"1991","unstructured":"Gerich, J. E., Mokan, M., Veneman, T., Korytkowski, M. & Mitrakou, A. Hypoglycemia unawareness. Endocr. Rev. 12, 356\u2013371 (1991).","journal-title":"Endocr. Rev."},{"key":"1424_CR68","doi-asserted-by":"publisher","unstructured":"Mendez, C. et al. Toward detection of nocturnal hypoglycemia in people with diabetes using consumer-grade smartwatches and a machine learning approach. J. Diabetes Sci. Technol. https:\/\/doi.org\/10.1177\/19322968251319800 (2025).","DOI":"10.1177\/19322968251319800"},{"key":"1424_CR69","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1007\/s12288-015-0514-5","volume":"32","author":"S Singh","year":"2016","unstructured":"Singh, S. et al. Gelatinous transformation of bone marrow: a prospective tertiary center study, indicating varying trends in epidemiology and pathogenesis. Indian J. Hematol. Blood Transfus. 32, 358\u2013360 (2016).","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"1424_CR70","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/j.molmet.2017.04.011","volume":"6","author":"AM D\u2019souza","year":"2017","unstructured":"D\u2019souza, A. M., Neumann, U. H., Glavas, M. M. & Kieffer, T. J. The glucoregulatory actions of leptin. Mol. Metab. 6, 1052\u20131065 (2017).","journal-title":"Mol. Metab."},{"key":"1424_CR71","doi-asserted-by":"publisher","first-page":"3990","DOI":"10.3390\/cancers13163990","volume":"13","author":"B Olson","year":"2021","unstructured":"Olson, B., Diba, P., Korzun, T. & Marks, D. L. Neural mechanisms of cancer cachexia. Cancers 13, 3990 (2021).","journal-title":"Cancers"},{"key":"1424_CR72","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/s41556-024-01386-y","volume":"26","author":"L Ding","year":"2024","unstructured":"Ding, L. et al. Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL. Nat. Cell Biol. 26, 552\u2013566 (2024).","journal-title":"Nat. Cell Biol."},{"key":"1424_CR73","doi-asserted-by":"publisher","first-page":"e160915","DOI":"10.1172\/jci.insight.160915","volume":"7","author":"Z Li","year":"2022","unstructured":"Li, Z. et al. Constitutive bone marrow adipocytes suppress local bone formation. JCI Insight 7, e160915 (2022).","journal-title":"JCI Insight"},{"key":"1424_CR74","doi-asserted-by":"publisher","first-page":"2468","DOI":"10.1046\/j.1471-4159.1998.70062468.x","volume":"70","author":"SA Thomas","year":"1998","unstructured":"Thomas, S. A., Marck, B. T., Palmiter, R. D. & Matsumoto, A. M. Restoration of norepinephrine and reversal of phenotypes in mice lacking dopamine beta-hydroxylase. J. Neurochem. 70, 2468\u20132476 (1998).","journal-title":"J. Neurochem."},{"key":"1424_CR75","doi-asserted-by":"publisher","first-page":"e175159","DOI":"10.1172\/jci.insight.175159","volume":"9","author":"JM Brazill","year":"2024","unstructured":"Brazill, J. M. et al. Sarm1 knockout prevents type 1 diabetic bone disease in females independent of neuropathy. JCI Insight 9, e175159 (2024).","journal-title":"JCI Insight"},{"key":"1424_CR76","doi-asserted-by":"publisher","unstructured":"DeVos, S. L. & Miller, T. M. Direct intraventricular delivery of drugs to the rodent central nervous system. J. Vis. Exp. https:\/\/doi.org\/10.3791\/50326 (2013).","DOI":"10.3791\/50326"},{"key":"1424_CR77","doi-asserted-by":"publisher","first-page":"C1609","DOI":"10.1152\/ajpcell.00441.2011","volume":"302","author":"GA Meyer","year":"2012","unstructured":"Meyer, G. A. & Lieber, R. L. Skeletal muscle fibrosis develops in response to desmin deletion. Am. J. Physiol. Cell Physiol. 302, C1609\u2013C1620 (2012).","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"1424_CR78","doi-asserted-by":"publisher","first-page":"ziaf006","DOI":"10.1093\/jbmrpl\/ziaf006","volume":"9","author":"AT Beeve","year":"2025","unstructured":"Beeve, A. T. et al. Spatial histomorphometry reveals that local peripheral nerves modulate but are not required for skeletal adaptation to applied load in mice. JBMR Plus 9, ziaf006 (2025).","journal-title":"JBMR Plus"},{"key":"1424_CR79","doi-asserted-by":"crossref","unstructured":"Lorenz, M., Brazill, J., Beeve, A., Shen, I. & Scheller, E. Spatial mapping and contextualization of axon subtypes innervating the long bones of C3H and B6 mice. SPARC Portal https:\/\/sparc.science\/datasets\/109?type=dataset (2021).","DOI":"10.1002\/jbmr.4273"},{"key":"1424_CR80","doi-asserted-by":"publisher","unstructured":"Beeve, A. T., Li, A., Hassan, M. G. & Scheller, E. L. Protocol for quantification of bone indices, calcein labels, and nerve axon density in multi-channel confocal images. protocols.io https:\/\/doi.org\/10.17504\/protocols.io.bp2l62b1dgqe\/v1 (2025).","DOI":"10.17504\/protocols.io.bp2l62b1dgqe\/v1"},{"key":"1424_CR81","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/B978-0-12-411619-1.00007-0","volume":"537","author":"EL Scheller","year":"2014","unstructured":"Scheller, E. L. et al. Use of osmium tetroxide staining with microcomputerized tomography to visualize and quantify bone marrow adipose tissue in vivo. Meth. Enzymol. 537, 123\u2013139 (2014).","journal-title":"Meth. Enzymol."},{"key":"1424_CR82","doi-asserted-by":"publisher","first-page":"e1865","DOI":"10.21769\/BioProtoc.1865","volume":"6","author":"Y Rinkevich","year":"2016","unstructured":"Rinkevich, Y. et al. Denervation of mouse lower hind limb by sciatic and femoral nerve transection. Bio Protoc. 6, e1865 (2016).","journal-title":"Bio Protoc."},{"key":"1424_CR83","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"1424_CR84","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","volume":"36","author":"SX Ge","year":"2020","unstructured":"Ge, S. X., Jung, D. & Yao, R. ShinyGO: a graphical gene-set enrichment tool for animals and plants. Bioinformatics 36, 2628\u20132629 (2020).","journal-title":"Bioinformatics"},{"key":"1424_CR85","doi-asserted-by":"publisher","first-page":"e72367","DOI":"10.1371\/journal.pone.0072367","volume":"8","author":"L-F Liu","year":"2013","unstructured":"Liu, L.-F. et al. Age-related modulation of the effects of obesity on gene expression profiles of mouse bone marrow and epididymal adipocytes. PLoS ONE 8, e72367 (2013).","journal-title":"PLoS ONE"},{"key":"1424_CR86","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1002\/jcp.26037","volume":"233","author":"D Mattiucci","year":"2018","unstructured":"Mattiucci, D. et al. Bone marrow adipocytes support hematopoietic stem cell survival. J. Cell. Physiol. 233, 1500\u20131511 (2018).","journal-title":"J. Cell. Physiol."},{"key":"1424_CR87","doi-asserted-by":"publisher","first-page":"3736","DOI":"10.1016\/S0021-9258(18)97104-8","volume":"240","author":"RY Hsu","year":"1965","unstructured":"Hsu, R. Y., Wasson, G. & Porter, J. W. The purification and properties of the fatty acid synthetase of pigeon liver. J. Biol. Chem. 240, 3736\u20133746 (1965).","journal-title":"J. Biol. Chem."},{"key":"1424_CR88","doi-asserted-by":"publisher","first-page":"e97076","DOI":"10.1172\/jci.insight.97076","volume":"3","author":"R Rajagopal","year":"2018","unstructured":"Rajagopal, R. et al. Retinal de novo lipogenesis coordinates neurotrophic signaling to maintain vision. JCI Insight 3, e97076 (2018).","journal-title":"JCI Insight"}],"container-title":["Nature Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42255-025-01424-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-025-01424-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42255-025-01424-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T13:03:39Z","timestamp":1769691819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42255-025-01424-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,8]]},"references-count":88,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["1424"],"URL":"https:\/\/doi.org\/10.1038\/s42255-025-01424-5","relation":{},"ISSN":["2522-5812"],"issn-type":[{"value":"2522-5812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,8]]},"assertion":[{"value":"18 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}